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Prenatal exposure to vapors of gasoline-ethanol blends causes few cognitive deficits in adult rats
Oshiro, W., T. Beasley, Kathy Mcdaniel, P. Evansky, S. Martin, V. C. Moser, M. Gilbert, AND P. Bushnell. Prenatal exposure to vapors of gasoline-ethanol blends causes few cognitive deficits in adult rats. NEUROTOXICOLOGY AND TERATOLOGY. Elsevier Science Ltd, New York, NY, 49:59-73, (2015).
A series of experiments in rats were conducted to address questions regarding the potential neurodevelopmental consequences of adding ethanol to gasoline. Thus, cognitive function tests were conducted in adult offspring of rat dams exposed during gestation to high concentrations of vapor condensates made from gasoline without ethanol (EO), and two gasoline-ethanol blends, of 15% and 85% ethanol in gasoline (E15 and E85). Inhaled vapors of fuel mixtures containing gasoline and ethanol exerted no systematically concentration-related adverse effects on the majority of cognitive tests conducted in this report. One test of reference memory showed impairments in E85 male offspring at concentrations 6000 ppm and choice reaction time tests showed transient increases in anticipatory responding in male offspring exposed to EO and E15 at concentrations6000 ppm, indicative of a response inhibition deficit. However this effect was transient and not confirmed in animals tested on a response inhibition task. The overall pattern of these results and our previous work with inhaled ethanol does not support a systematic change in toxicity with increasing ethanol content of the vapor. These results will inform OTAQ's assessment of ethanol as a component of automotive fuels.
Developmental exposure to inhaled ethanol-gasoline fuel blends is a potential public health concern. Here we assessed cognitive functions in adult offspring of pregnant rats that were exposed to vapors of gasoline blended with a range of ethanol concentrations, including gasoline alone (EO) and gasoline with 15% or 85% ethanol (E15 and EB5, respectively) Rat dams were exposed for 6.5h daily to the vapors at concentrations of 0,3000,6000, or 9000ppm in inhalation chambers from gestational day (GD) 9 through 20. Cage controls (offspring of non-exposed dams that remained in the animal facility during these exposures) were also assessed in the EO experiment, but showed no consistent differences from the offspring of air-exposed controls. Offspring were tested as adults with trace fear conditioning, Morris water maze, or appetitive operant responding. With fear conditioning, no significant effects were observed on cue or context learning. In the water maze, there were no differences in place learning or escaping to a visible platform. However, during the reference memory probe (no platform) male rats exposedprenatally to E85 vapor (6000 and 9000ppn) failed to show a bias for the target quadrant. Across studies, females (treated and some controls) were less consistent in this measure. Males showed no differences during match-to-place learning (platform moved each day) in any experiment and females showed only transient differences in latency and path length in the EO experiment. Similarly, no differences were observed in delayed match-to-sample operant performance of EO males or females; thus this test was not used to evaluate effects of E15 or E85 vapors. During choice reaction time assessments (only males were tested) decision and movement times were unimpaired by any prenatal exposure, while anticipatory responses were increased by vapors of EO (9000ppm) and E15 (6000 and 9000ppm), and the latter group also showed reduced accuracy. E85 vapors did not disrupt any choice reaction time measure. Finally, no response inhibition deficit was observed in a differential reinforcement of low rate (DRL) response schedule in males or females in the E15 or E85 experiments. In summary, prenatal exposure to these fuel blends produced few deficits in adult offspring on these cognitive tests. Significant effects found during a water maze probe trial and choice reaction time tests were observed at vapor concentrations of 6000ppm or higher, a concentration that is 4-6 orders of magnitude higher than those associated with normal automotive fueling operations and garages. Similar effects were not consistently observed in a previous study of inhaled ethanol, and thus these effects cannot be attributed to the concentration of ethanol in the mixture.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
TOXICOLOGY ASSESSMENT DIVISION